Fibrocartilage is a specialized tissue sharing characteristics of fibrous tissue and, to various degrees, cartilage. Fibrocartilage consists of a mixture of white fibrous tissue and cartilaginous tissue in various proportions. It owes its flexibility and toughness to fibrous tissue, and its elasticity to cartilaginous tissue. Fibrocartilage is the only type of cartilage that contains type I collagen in addition to the normal type II.
In humans, fibrocartilage is found in knee meniscus, ligament/tendon insertion to bone, the intervertebra disc (IVD), and the temporomandibular joint (TMJ). All fibrocartilage tissues are intrinsically recalcitrant to regeneration. Few therapies exist to regenerate fibrocartilage tissues.
Cells of fibrocartilage are not well understood but are frequently referred to as fibrochondrocytes. Although mesenchymal stem cells (MSCs) are the presumably source of fibrochondrocytes in development, there is little evidence that postnatal fibrochondrocytes derive from postnatal MSCs. In comparison with known and recently demonstrated pathways of osteogenic, chondrogenic, and adipogenic differentiation, little is known about the induction cues and signaling pathways for fibrochondrogenic differentiation. It has been reported that connective tissue growth factor (CTGF) alone induces fibroblastic differentiation of MSCs (Lee et al. 2010 J Clin Investig (in press). It has also been reported that CTGF-mediated fibrogenesis is regulated by a separate signaling pathway from transforming growth factor β3 (TGFβ3)-mediated chondrogenesis (Tuli et al. 2003 J Biol Cem 17(278), 41227-41236).
Prior to the present disclosure, there existed no reliable way to differentiate stem cells or progenitor cells into fibrochondrocytes. Conventional methods utilize cyclic mechanical stimulus to induce fibrochondrogenic differentiation but yields unreliable cells.